Reliable Measurements of theβ-Amyloid Pool in Blood Could Help in the Early Diagnosis of AD

Abstract

The present study was aimed at assessing the capability of Aβ1-40 and Aβ1-42 levels in undiluted plasma (UP), diluted plasma (DP), and cell bound (CB) to distinguish between early stages of Alzheimer's disease (AD), amnesic mild cognitive impairment (MCI), and healthy control (HC). Four blood samples from each participant were collected during one month and the levels of Aβ1-40 and Aβ1-42 were determined by a blinded proprietary ELISA sandwich (Araclon Biotech. Zaragoza, Spain). First striking result was that the amount of Aβ1-40 and Aβ1-42 in UP represented only a small proportion (~15%) of the total beta-amyloid pool in blood (βAPB) described here as the sum of Aβ1-40 and Aβ1-42 in blood where they are free in plasma, bound to plasma proteins, and bound to blood cells. Furthermore, we found that levels of Aβ1-40 and Aβ1-42 in UP, DP, and CB were significantly higher in MCI when compared to HC. On average, the total βAPB was 1.8 times higher in MCI than in HC (P = 0.03) and allowed to discriminate between MCI and HC with a sensitivity and specificity over 80%. Thus, quantification of several markers of the βAPB could be useful and reliable in the discrimination between MCI and HC.

Plasma amyloid‐β and risk of Alzheimer's disease in the Framingham Heart Study

“…Differences in blood sampling (fasting versus non fasting, time of the day, tube used for collecting blood) and storage protocols may account for a substantial portion of the observed heterogeneity [16]. Moreover, assays may differ in their capacity to capture Aβ peptides, and most of them can only detect free, circulating monomers, which represent less than 50% of all circulating Aβ peptides [39]. Finally, sample size, follow-up time and analysis strategies may also generate differences in association estimates.…”

A truncated and dimeric format of an Affibody library on bacteria enables FACS‐mediated isolation of amyloid‐beta aggregation inhibitors with subnanomolar affinity

“…It has been shown that there is a correlation between the affinity of peripherally-administered Ab-specific agents and the efflux of Ab from the brain to the serum [29]. As levels of Ab peptides in the blood are low (subnanomolar) [30][31][32][33][34], it is probably critical to use capturing-agents of high affinity for such applications.…”

“…It has been shown that there is a correlation between the affinity of peripherally-administered Ab-specific agents and the efflux of Ab from the brain to the serum [29]. As levels of Ab peptides in the blood are low (subnanomolar) [30][31][32][33][34], it is probably critical to use capturing-agents of high affinity for such applications.It has previously been demonstrated that staphylococcal cell surface display in combination with fluorescenceactivated cell sorting (FACS) is well suited for combinatorial affinity maturation efforts, since it allows for high precision affinity discrimination between binders [35][36][37][38]. Recently, the method was used for affinity maturation of a HER3-specific Affibody, and generated binders with picomolar affinities [39].…”

Interactions of β-amyloid peptide with fibrinogen and coagulation factor XII may contribute to Alzheimer's disease

“…As Aβ is cleared from the brain, it can access extracellular fluids like cerebrospinal fluid (CSF) and blood [5], which would bring it in contact with plasma proteins. Since much of the Aβ produced in the brain is cleared through the cerebral vasculature, Aβ levels are higher in CNS venous blood compared to arterial blood [6] with some studies showing that elevated plasma Aβ levels are an early event in AD development [7, 8]. During clearance, Aβ can also accumulate around blood vessels as cerebral amyloid angiopathy (CAA).…”